SUMO促进创伤性颅脑损伤神经修复的研究

The high mortality and morbidity after traumatic brain injury (TBI) threaten the public health. We devote to promoting restoration of nervous system by improving the self-protection of injured cells and endogenous neurogenesis of stem cells. SUMO (Small ubiquitin-like modifier) is a group of proteins, which could conjugate to the target protein to regulate the post-translational process and regulate plenty of signaling pathway. The ischemia-induced activation of SUMO conjugation is shown to be a protective response of post-ischemic neurons. We hypothesize that SUMO has a neuroprotective effect after TBI. Our group observed the sumoylation in the territory border, hippocampus and ventricular zone from the ipsilateral hemispheres after TBI. We also found the sumoylation both in neuron and astrocyte. We will detect the SUMO expression following injury and use SUMO knockdown transgenic mice to observe SUMO function for nervous repair after TBI. Finally, we will detect the main gene and signaling pathway related to sumoylation after TBI. These researches will provide some basic theory toward further study for molecular mechanism and drug therapy, which will be as a candidate for future neurotherapeutic intervention following TBI.

脑外伤后有较高的致死及致残率,我们致力于提高损伤细胞的自我保护机制以及内源性神经再生的能力来促进神经修复。SUMO(Small ubiquitin-like modifier)是一种类似于泛素的蛋白质,发挥蛋白质翻译后修饰的作用, 能够调节多种信号通路，在缺血性脑损伤中有明确的细胞保护作用，我们首次提出SUMO在脑创伤后也必定发挥多通道的神经保护作用。本课题组前期研究发现,在创伤灶周围和创伤侧海马及脑室呈现出明显的SUMO化现象；创伤灶周围的神经元和星形胶质细胞中都存在SUMO化现象。接下来,我们将全面检测脑外伤后SUMO的表达,并运用SUMO敲低的转基因小鼠来研究SUMO在脑外伤后神经修复的作用,最后运用Microarray分析的方法发现脑创伤后SUMO调节的主要基因及信号转导通路。为后续研究SUMO在脑创伤中发挥神经修复作用的分子机制及药物开发奠定基础,为临床治疗脑创伤提供新思路。

脑外伤后有较高的致死及致残率,我们致力于提高损伤细胞的自我保护机制以及内源性神经再生的能力来促进神经修复。SUMO(Small ubiquitin-like modifier)是一种类似于泛素的蛋白质,发挥蛋白质翻译后修饰的作用, 能够调节多种信号通路，在缺血性脑损伤中有明确的细胞保护作用，我们首次提出SUMO在脑创伤后也必定发挥多通道的神经保护作用。本项目研究发现,在创伤灶周围呈现出明显的SUMO化现象；创伤灶周围的神经元和星形胶质细胞中都存在SUMO化现象。本项目全面检测脑外伤后SUMO的表达,并运用SUMO敲低的转基因小鼠来研究SUMO在脑外伤后的作用,发现SUMO敲低的转基因小鼠脑外伤后创伤灶周围的凋亡细胞明显高于野生型小鼠。最后运用Microarray分析的方法发现脑创伤后SUMO在创伤早期参与免疫、炎症反应及细胞凋亡多个生物学过程，为脑创伤的研究提出了新方向，对今后临床治疗脑创伤有指导意义。